Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

Aims: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring (CGM) metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants. Methods: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by CGM measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration 97.7th centile (63.2% vs 33.9%; p<0.0001) and skinfold thickness (p≤0.02). Intrapartum CGM was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia. Conclusions: Modest increments in CGM time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum CGM data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia, suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period

Building Consensus for a Shared Definition of Adverse Events: A Case Study in the Profession of Dentistry

BACKGROUND: To achieve high-quality health care, adverse events (AEs) must be proactively recognized and mitigated. However, there is often ambiguity in applying guidelines and definitions. We describe the iterative calibration process needed to achieve a shared definition of AEs in dentistry. Our alignment process includes both independent and consensus building approaches. OBJECTIVE: We explore the process of defining dental AEs and the steps necessary to achieve alignment across different care providers. METHODS: Teams from 4 dental institutions across the United States iteratively reviewed patient records after identification of charts using an automated trigger tool. Calibration across teams was supported through negotiated definition of AEs and standardization of evidence provided in review. Interrater reliability was assessed using descriptive and κ statistics. RESULTS: After 5 iterative cycles of calibration, the teams (n = 8 raters) identified 118 cases. The average percent agreement for AE determination was 82.2%. Furthermore, the average, pairwise prevalence and bias-adjusted κ (PABAK) was 57.5% (κ = 0.575) for determining AE presence. The average percent agreement for categorization of the AE type was 78.5%, whereas the PABAK was 48.8%. Lastly, the average percent agreement for categorization of AE severity was 82.2% and the corresponding PABAK was 71.7%. CONCLUSIONS: Successful calibration across reviewers is possible after consensus building procedures. Higher levels of agreement were found when categorizing severity (of identified events) rather than the events themselves. Our results demonstrate the need for collaborative procedures as well as training for the identification and severity rating of AEs

Layers of advocacy: How librarians everywhere can make a difference and lessons for LIS education

Lobbying and advocacy are critical to the success of libraries, because they play a key role in communicating to decision-makers and communities why libraries are essential resources in an information-driven society. However, despite the importance of lobbying and advocacy to the profession, it is not always clear how library schools should teach about this aspect of librarianship. Taking an international, comparative approach, this panel discusses the complexities associated with lobbying and advocacy, as well as some challenges faced by LIS educators when teaching about the topic. To make teaching about lobbying and advocacy in LIS easier, six panelists with experience in a range of political, social, and cultural contexts will talk about issues such as: levels of government where lobbying takes place; varying definitions of advocacy, especially across countries with different traditions of librarianship; and the time frame in which lobbying and advocacy efforts take place. Panelist presentations will emphasize “lessons learned” that can be used to teach LIS students how to cultivate support for libraries. Using panelist presentations as a starting point, this panel will include a follow-up discussion about teaching advocacy in LIS. A primary goal of this panel is to identify powerful content for LIS curricula and instructional approaches that can support more effective advocacy. We will conclude by opening the door to audience participation with the purpose of integrating new ideas into the discussion.This material is based upon work supported by the U.S. National Science Foundation under Grant No. 182222

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Metabolomic insights into maternal and neonatal complications in type 1 diabetes pregnancies

Aims: Type 1 diabetes (T1D) in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (preeclampsia, large-for-gestational-age (LGA), neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in women with Type 1 Diabetes in pregnancy trial (CONCEPTT). Methods: 174 CONCEPTT participants gave >1 non-fasting serum sample for the biorepository at 12wks (147 women), 24wks (167 women) and 34wks (160 women) with cord blood on 93 infants. Results from metabolite analysis (ultrahigh performance liquid chromatography – mass spectrometry; Metabolon, Germany) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. Results: Maternal CGM time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triglycerides in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia, and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triglycerides or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24wks. Conclusions/ interpretation: Altered lipid metabolism is a key pathophysiological feature of T1D pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in T1D.This project was funded by Diabetes UK (PG 2017/2278). The CONCEPTT trial was funded by Juvenile Diabetes Research Foundation (JDRF) grants #17‐2011‐533, and grants under the JDRF Canadian Clinical Trial Network, a public‐private partnership including JDRF and FedDev Ontario and supported by JDRF #80‐2010‐585. Medtronic supplied the CGM sensors and CGM systems at reduced cost. The study sponsor/funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712), a BMA Foundation Award (Helen H Lawson Award) and the European Foundation for the Study of Diabetes – Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974). HRM conducts independent research supported by the National Institute for Health Research (Career Development Fellowship, CDF-2013-06-035), and is supported by Tommy’s charity. SF and AK acknowledge funding from the BBSRC (BB/M027252/1). DSF conducts independent research supported by the Canadian Institute for Health Research. This research was supported by the NIHR Cambridge BRC, the core biochemical assay laboratory (CBAL) and the core metabolomic and lipidomic laboratory (CMAL). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

Comparing a Computer-based Childhood Vaccination Registry with Parental Vaccination Cards: A Population-based Study of Delaware Children

We conducted a population-based study in Delaware to examine the reliability of childhood vaccination data in a comprehensive computer-based record system versus parental vaccination cards. We sampled 1,005 children born betweenJanuary, 1991, and September, 1993. We oversampled for children whose mothers received Medicaid or were uninsured at the time of delivery. Of the survey responders, 276 (56%) had access to written records, and 409 (83%) records were located in the Delaware immunization computer database. The kappa coefficient was 0.18. The observed agreement was 59.8%. When the two databases were combined, the up-to-date rate for 2-year-olds was 58.4%, an increase of 12.7% and 24.2% from the computer database and the parental records, respectively. The computer database was 78.1% sensitive and the parental records were 54.9% sensitive. These results indicate that a comprehensive computer-based record system, with adequate provider participation and proper data management, can be more reliable than parental vaccination cards.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67546/2/10.1177_000992289703600406.pd

Metabolomic insights into maternal and neonatal complications in pregnancies affected by type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). METHODS: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. RESULTS: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. CONCLUSIONS/INTERPRETATION: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes